{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T19:34:29Z","timestamp":1786649669631,"version":"build-2736575974"},"reference-count":16,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>\n                    A\n                    <jats:sc>BSTRACT<\/jats:sc>\n                  <\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>We aimed to identify the early-onset Alzheimer\u2019s disease (EOAD)-causing variants in the Eastern Taiwanese population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods:<\/jats:title>\n                    <jats:p>Twenty-one patients diagnosed with EOAD in the memory clinic at Hualien Tzu Chi Hospital were enrolled during 2014\u20132018. We conducted whole-exome sequencing to identify the disease-causing variations and validated by Sanger sequencing. SIFT, PolyPhen-2, and AlphaFold were applied to predict the functional impact of the identified variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Two unrelated normolipidemic EOAD patients were carrying a rare heterozygous\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      variant (\n                      <jats:italic toggle=\"yes\">rs373985746<\/jats:italic>\n                      , NC_000019.10:g. 44905879\n                      <jats:italic toggle=\"yes\">G&gt;A<\/jats:italic>\n                      , NM_001302688.2:c. 11\n                      <jats:italic toggle=\"yes\">G<\/jats:italic>\n                      &gt;\n                      <jats:italic toggle=\"yes\">A<\/jats:italic>\n                      , and NP_001289617.1:p.Gly4Glu) with the allele frequency as 0.000206. Sanger sequencing uncovered the \u2211 haplotypes in which the c.11G&gt;A variation resided. SIFT predicted that the variant severely impacts protein structure and, maybe thus, function. AlphaFold predicted a dysfunctional conformation of the mutant APOE precursor a protein (p.Gly4Glu).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Our data strongly suggest that the rare p.Gly4Glu variant is associated with EOAD but does not cause dyslipidemia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.4103\/tcmj.tcmj_117_24","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T02:03:55Z","timestamp":1743991435000},"page":"175-180","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Rare APOE p.Gly4Glu: A putative disease-causing variant for early-onset Alzheimer\u2019s disease identified by next-generation sequencing"],"prefix":"10.4103","volume":"37","author":[{"given":"Chu-Ting","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Medicine, Tzu Chi University, Hualien, Taiwan"},{"name":"Department of Family Medicine, Puli Christian Hospital, Nantou, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang-Hsuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Ying","family":"Weng","sequence":"additional","affiliation":[{"name":"Biomedical Industry Ph.D. Program, National Yang Ming Chiao Tung University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Ming","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Genomic Medicine, National Health Research Institute, Miaoli, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung-Feng","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Genomic Medicine, National Health Research Institute, Miaoli, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Feng","family":"Tsai","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Genomic Medicine, National Health Research Institute, Miaoli, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond Y.","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Taitung St. Mary\u2019s Hospital, Taitung, Taiwan"},{"name":"Department of Neurology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan"},{"name":"Department of Biochemistry and Molecular Medicine, National Dong Hwa University, Hualien, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung-Hao","family":"Ching","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,4,7]]},"reference":[{"key":"R3-20250407","first-page":"1","article-title":"World Alzheimer Report 2009: The Global Prevalence of Dementia. 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